Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

A new look at the origins of gibbon ape leukemia virus.

Is the origin of gibbon ape leukemia virus (GALV) human after all? When GALV was discovered and found to cause neoplastic disease in gibbons, it stimulated a great deal of research including investigations into the origins of this virus. A number of publications have suggested that the GALV progenitor was a retrovirus present in one of several species of South East Asian rodents that had close contact with captive gibbons. However, there are no published retroviral sequences from any South East Asian species to support this view. Here we present an alternative hypothesis that the origin of GALV is a virus closely related to Melomys burtoni retrovirus, and that this virus infected human patients in Papua New Guinea from whom biological material was obtained or in some way contaminated these samples. This material we propose contained infectious MbRV-related virus that was then unwittingly introduced into gibbons which subsequently developed GALV infections.

Randomised controlled trial comparing marksmanship following application of a tourniquet or haemostatic clamp in healthy volunteers.

BACKGROUND: In a care under fire situation, a first line response to haemorrhage is to apply a tourniquet and return fire. However, there is little understanding of how tourniquets and other haemorrhage control devices impact marksmanship. METHODS: We compared the impact of the iTClamp and the Combat Application Tourniquet (CAT) on marksmanship. Following randomisation (iTClamp or CAT), trained marksmen fired an AR15 at a scaled silhouette target in prone unsupported position (shooting task). Subjects then attempted to complete the shooting task at 5, 10, 15, 30 and 60 min post-haemorrhage control device application. RESULTS: All of the clamp groups (n=7) completed the 60 min shooting task. Five CAT groups (n=6) completed the 5 min shooting task and one completed the 5 and 10 min shooting task before withdrawing. Four CAT groups were stopped due to unsafe handling; two stopped due to pain. When examining hits on mass (HOM) for the entire shooting task, there was no significant difference between tourniquet and iTClamp HOM at 5 min (p=0.18). However, there was a significant difference at 10 min, p=0.003 with tourniquet having significantly fewer HOM (1.7±2.7 HOM) than the iTClamp (8.1±3.3 HOM) group. The total effective HOM for the entire 60 min shooting task showed that the iTClamp group achieved significantly (p=0.001) more HOM than the tourniquet group. Over the entire 60 min shooting exercise, the iTClamp group achieved a median 72% (52/72) of available HOM while the tourniquet group obtained 19% (14/72). CONCLUSIONS: Application of a tourniquet to the dominant arm negates effective return of fire in a care under fire setting after a brief time window. Haemorrhage control devices that preserve function may have a role in care under fire situations, as preserving effectiveness in returning fire has obvious operational merits.

Laser induced fluorescence measurements of axial velocity, velocity shear, and parallel ion temperature profiles during the route to plasma turbulence in a linear magnetized plasma device.

We report experimental measurements of the axial plasma flow and the parallel ion temperature in a magnetized linear plasma device. We used laser induced fluorescence to measure Doppler resolved ion velocity distribution functions in argon plasma to obtain spatially resolved axial velocities and parallel ion temperatures. We also show changes in the parallel velocity profiles during the transition from resistive drift wave dominated plasma to a state of weak turbulence driven by multiple plasma instabilities.

Quality of in-home care, long-term care placement, and the survival of persons with dementia.

PURPOSE OF THE STUDY: Caregivers of persons with dementia living at home adopt a variety of caregiving styles that vary in quality. Three styles of high-quality care and poor-quality care have been identified. The outcomes, however, of varying styles of caregiving are unknown. Our purpose was to investigate the linkage of quality of care to long-term care placement and survival. DESIGN AND METHODS: We used a sample of 148 primary caregivers of a relative living at home and needing assistance due to memory or thinking problems. We used items from four existing scales and five new items to construct measures of high-quality and poor-quality care. Long-term care and survival were determined from two follow-ups. Cox proportional hazards regression was used to estimate the relationship of quality of care to long-term care placement and survival. RESULTS: Poor quality of care increased the risk of long-term care placement, as expected, but high-quality care was not related to placement. Surprisingly, high-quality care increased the risk of death while poor-quality care decreased the risk. Secondary results were: wishful/intrapsychic coping (a dysfunctional type of emotion-focused coping) and long-term care placement shortened the survival; and caregiver personality traits of neuroticism and agreeableness lengthened the survival. IMPLICATIONS: It is premature to recommend caregiver interventions based on our unexpected findings. Further studies are vital and should include care-recipient impairments and the quality of life of the person with dementia as additional outcomes.

Effects of toluene, acrolein and vinyl chloride on motor activity of Drosophila melanogaster.

The data generated by current high-throughput assays for chemical toxicity require information to link effects at molecular targets to adverse outcomes in whole animals. In addition, more efficient methods for testing volatile chemicals are needed. Here we begin to address these issues by determining the utility of measuring behavioral responses of Drosophila melanogaster to airborne volatile organic compounds (VOCs) as a potential model system for discovering adverse outcome pathways and as a method to test for toxicity. In these experiments, we measured motor activity in male and female flies to determine concentration-effect functions for three VOCs that differ in their mode of action: toluene, a narcotic; acrolein, an irritant; and vinyl chloride, a hepatocarcinogen. These experiments were conducted in Flyland, an outbred population of flies derived from 40 lines of the Drosophila Genetics Reference Panel (DGRP) (Mackay et al., 2012), in preparation for subsequent experiments with individual lines of the DGRP. Systematic, concentration-related changes in activity were observed with toluene, but not with acrolein; high concentrations of vinyl chloride reduced activity by a small amount. Despite higher activity levels in males than in females under control conditions, the sexes were equally sensitive to toluene. Transient increases in activity at the onset and offset of exposure to toluene and vinyl chloride suggested that the flies detected changes in air quality at concentrations that did not persistently suppress activity. The effects and potency of toluene are consistent with those observed in rodents. The lack of clear concentration-related changes in response to acrolein and vinyl chloride shows limitations of this method is for screening toxicity attributed to VOCs. This abstract does not reflect U.S. EPA policy.

Optimization of confocal laser induced fluorescence in a plasma.

Laser Induced Fluorescence (LIF) provides measurements of flow speed, temperature, and density of ions or neutrals in a plasma. Traditionally, a LIF measurement requires two ports on a plasma device; one for laser injection and one for emission collection. Proper alignment of LIF optics is time consuming and sensitive to mechanical vibration. We describe a confocal configuration for LIF that requires a single port and requires no alignment. The measurement location is scanned radially by physically moving the entire optical structure. Confocal LIF measurements are compared to traditional LIF measurements over the same radial range.

Prevalence and Cognitive Bases of Subjective Memory Complaints in Older Adults: Evidence from a Community Sample.

Objectives. To estimate the prevalence of subjective memory complaints (SMCs) in a sample of community-dwelling, older adults and to examine cognitive bases of these complaints. Participants. 499 community-dwelling adults, 65 and older. Measurements. A telephone survey consisting of cognitive tests and clinical and sociodemographic variables. SMCs were based on subjects' evaluations and subjects' perceptions of others' evaluations. Analysis. Logistic regression was used to model the risk for SMCs as a function of the cognitive, clinical, and sociodemographic variables. We tested for interactions of the cognitive variables with age, education, and gender. Results. 27.1% reported memory complaints. Among the younger age, better objective memory performance predicted lower risk for SMCs, while among the older age, better memory had no effect on risk. Among the better-educated people, better global cognitive functioning predicted lower risk for SMCs, while among the less-educated people, better global cognitive functioning had no effect on SMC risk. When predicting others' perceptions, better objective memory was associated with lower risk for SMCs. Conclusion. Objective memory performance and global cognitive functioning are associated with lower risk for SMCs, but these relationships are the strongest for the younger age and those with more education, respectively. Age and education may affect the ability to accurately appraise cognitive functioning.

Quality of informal care for persons with dementia: dimensions and correlates.

OBJECTIVES: The majority of persons with dementia live in the community where most of their care is provided by family members. We aimed to expand our limited knowledge about the styles of high-quality care, such as person-centered care, and poor-quality care adopted by these informal caregivers and the characteristics of those who provide better care. METHOD: We conducted a mail survey of 148 family caregivers. Caregiving styles were measured with items from existing scales that had not been analyzed together before. Factor analysis of these items was used to identify styles of caregiving, and structural equation modeling was used to identify their relationships with caregiver and care-recipient characteristics. RESULTS: Three high quality-of-care factors (personalized, respectful, and compensatory) and three poor quality-of-care factors (punitive, controlling, and withdrawing) were found. The personality traits of agreeableness, openness, conscientiousness, and neuroticism were related to higher quality of care, and the trait of extraversion was related to poorer quality of care. Wishful coping - an avoidance/escape strategy - was linked to poorer quality of care. CONCLUSION: We discovered new dimensions of quality of care, some consistent with person-centered care and some antithetical to this model, and we identified for the first time caregiver personality traits and coping strategies associated with better quality of care. These results may be useful in targeting caregiver interventions to benefit both caregivers and care recipients.

The DrivingHealth® Inventory as a clinical screening tool-assessment of face validity and acceptance.

To investigate the use and potential for patient acceptance of the DrivingHealth(®) Inventory (DHI) in clinical practice, we administered the DHI to 360 community dwelling volunteers over age 50 at a Southeastern US rehabilitation hospital. Volunteers also completed surveys to document their health, driving habits, and impressions of the DHI. Volunteers reported strong agreement with statements that indicated that they believe the DHI measures abilities important for safe driving and that they would be willing to listen to advice about driving and safe mobility from medical professionals; however, responses to some items were more positive among drivers whose DHI results indicated no apparent loss of function that could impair driving. These results support the use of the DHI in clinical practice as a tool to raise awareness of factors that correlate to driving; however, further research will be necessary to investigate how the DHI may benefit diverse clinical populations. Experiences with using DHI as part of clinical practice are also discussed.

Prevalence of koala retrovirus in geographically diverse populations in Australia.

OBJECTIVE: To determine the prevalence of koala retrovirus (KoRV) in selected koala populations and to estimate proviral copy number in a subset of koalas. METHODS: Blood or tissue samples from 708 koalas in Queensland, New South Wales, Victoria and South Australia were tested for KoRV pol provirus gene using standard polymerase chain reaction (PCR), nested PCR and real-time PCR (qPCR). RESULTS: Prevalence of KoRV provirus-positive koalas was 100% in four regions of Queensland and New South Wales, 72.2% in mainland Victoria, 26.6% on four Victorian islands and 14.8% on Kangaroo Island, South Australia. Estimated proviral copy number per cell in four groups of koalas from Queensland and Victoria showed marked variation, ranging from a mean of 165 copies per cell in the Queensland group to 1.29 × 10(-4) copies per cell in one group of Victorian koalas. CONCLUSIONS: The higher prevalence of KoRV-positive koalas in the north of Australia and high proviral loads in Queensland koalas may indicate KoRV entered and became endogenous in the north and is spreading southwards. It is also possible there are genetic differences between koalas in northern and southern Australia that affect susceptibility to KoRV infection or endogenisation, or that environmental factors affecting transmission in northern states are absent or uncommon in southern regions. Although further studies are required, the finding of proviral copy numbers orders of magnitude lower than what would be expected for the presence of a single copy in every cell for many Victorian animals suggests that KoRV is not endogenous in these animals and likely reflects ongoing exogenous infection.

An inexpensive system for evaluating the tussive and anti-tussive properties of chemicals in conscious, unrestrained guinea pigs.

INTRODUCTION: Commercial whole-body plethysmography systems used to evaluate the anti-tussive potential of drugs employ sophisticated technology, but these systems may be cost prohibitive for some laboratories. The present study describes an alternative, inexpensive system for evaluating the tussive and anti-tussive potential of drugs in conscious, unrestrained guinea pigs. METHODS: The system is composed of a transparent small animal anesthesia induction box fitted with a microphone, a camera and a pneumotachometer to simultaneously capture audio, video, air flow and air pressure in real time. Data acquisition and analysis was performed using free software for audio and video, and a research pneumotach system for flow and pressure. System suitability testing was performed by exposing conscious, unrestrained guinea pigs to nebulized aqueous solutions of a selective agonist for TRPV1 (citric acid) or a selective agonist for TRPA1 (AITC), with or without pre-treatment with a selective antagonist for TRPV1 (BCTC) or a selective antagonist for TRPA1 (HC-030031). RESULTS: The system easily discerned coughs from other respiratory events like sneezes. System suitability test results are as follows: AITC caused 10.7 (SEM=1.4592) coughs vs. 5.8 (SEM=1.6553) when pre-treated with HC-030031 (P<0.05). Citric acid caused 12.4 (SEM=1.4697) coughs vs. 3.2 (SEM=1.3928) when pre-treated with BCTC (P<0.002). DISCUSSION: We have described in detail an inexpensive system for evaluating the tussive and anti-tussive potential of chemicals in conscious, unrestrained guinea pigs. Suitability testing indicates that the system is comparable to a commercial whole-body plethysmography system for detecting and differentiating between coughs and sneezes. This system may provide some investigators a cost-conscious alternative to more expensive commercial whole-body plethysmography systems.

Reanalyses of the historical series of UK variety trials to quantify the contributions of genetic and environmental factors to trends and variability in yield over time.

Historical datasets have much to offer. We analyse data from winter wheat, spring and winter barley, oil seed rape, sugar beet and forage maize from the UK National List and Recommended List trials over the period 1948-2007. We find that since 1982, for the cereal crops and oil seed rape, at least 88% of the improvement in yield is attributable to genetic improvement, with little evidence that changes in agronomy have improved yields. In contrast, in the same time period, plant breeding and changes in agronomy have contributed almost equally to increased yields of forage maize and sugar beet. For the cereals prior to 1982, contributions from plant breeding were 42, 60 and 86% for winter barley, winter wheat and spring barley, respectively. These results demonstrate the overwhelming importance of plant breeding in increasing crop productivity in the UK. Winter wheat data are analysed in more detail to exemplify the use of historical data series to study and detect disease resistance breakdown, sensitivity of varieties to climatic factors, and also to test methods of genomic selection. We show that breakdown of disease resistance can cause biased estimates of variety and year effects, but that comparison of results between fungicide treated and untreated trials over years may be a means to screen for durable resistance. We find the greatest sensitivities of the winter wheat germplasm to seasonal differences in rainfall and temperature are to summer rainfall and winter temperature. Finally, for genomic selection, correlations between observed and predicted yield ranged from 0.17 to 0.83. The high correlation resulted from markers predicting kinship amongst lines rather than tagging multiple QTL. We believe the full value of these data will come from exploiting links with other experiments and experimental populations. However, not to exploit such valuable historical datasets is wasteful.

A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease.

OBJECTIVES: To evaluate the safety of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in nondiabetic patients with Alzheimer disease (AD) and to explore treatment effect sizes on clinical outcomes. DESIGN: Double-blind, placebo-controlled randomized controlled trial of 18-month duration. SETTING: Two academic medical center outpatient clinics. PATIENTS: Nondiabetic patients meeting research criteria for probable AD were enrolled. Twenty-five of 29 subjects completed the study; no withdrawals were attributable to adverse effects. INTERVENTION: Subjects received pioglitazone (Actos), titrated to 45 mg daily, or matching placebo, and 200 IU of vitamin E daily. Patients maintained treatment with cholinesterase inhibitors and could begin memantine therapy when it became available during the study. MAIN OUTCOME MEASURES: The primary outcome was frequency of reported adverse effects (AEs). Secondary outcomes were measures of cognition, activities of daily living, neuropsychiatric symptoms, and global function. RESULTS: Peripheral edema was the principal AE occurring more frequently in subjects taking pioglitazone than placebo (28.6% vs 0%). This is consistent with the known AE profile of pioglitazone. No group differences in laboratory measures were identified. No significant treatment effect was observed on exploratory analysis of clinical efficacy. CONCLUSIONS: Pioglitazone was generally well tolerated in this pilot study. There were no serious or unanticipated adverse events or clinical laboratory changes attributable to pioglitazone over a long-term exposure in nondiabetic patients with AD. The tolerability of pioglitazone in this population and peroxisome proliferator-activated receptor gamma effects in laboratory models of AD support further study of this drug class in earlier disease stages. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00982202.

Pharmacological treatment of Alzheimer's disease: effect of race and demographic variables.

Existing research shows differences in medication use for Alzheimer's disease (AD) based on demographics such as race, ethnicity, and geographical location. To determine individual and community characteristics associated with differences in acetylcholinesterase inhibitor (AChEI) and memantine use in AD, 3,049 AD subjects were drawn from 30 centers and evaluated using the Uniform data set (UDS). Cases were evaluated at the individual level within the context of 31 communities (one center encompassed two separate geographical regions). Multivariate analysis was used to determine the significance of individual variables on medication use. Compared to non-Hispanic Whites, Blacks were less likely to use AChEI and memantine with odds ratios (OR) of 0.59 (95% CI 0.46-0.76) and 0.43 (95% CI 0.32-0.57), respectively. Compared to non-Hispanic Whites, non-Black Hispanics were less likely to use memantine (OR=0.69 (95% CI 0.49-0.98)). No association was found between the proportion of Blacks or non-Black Hispanics versus non-Hispanic Whites at an Alzheimer Disease Center and individual use of AChEI or memantine. Other significant variables include gender, age, marital status, dementia severity, source of referral, AChEI use, and education. Education and age somewhat mitigated disparity. Significant racial and ethnic differences in AChEI and memantine use exist at the individual level regardless of the racial and ethnic composition of the individual's community. Research and initiatives at the societal level may be an important consideration toward addressing these differences.

Memantine and acetylcholinesterase inhibitor treatment in cases of CDR 0.5 or questionable impairment.

The biological meaning of uncertain dementia ratings (CDR 0.5) and its treatment implications are unclear. Our study examines the frequency of anti-dementia medication use in individuals with CDR 0.5 and the cognitive, behavioral, and demographic factors associated with memantine and acetylcholinesterase inhibitor (AChEI) use. Subjects were drawn from the National Alzheimer Coordinating Center database, which collects data from 30 Alzheimer Disease Centers. There were 2,512 subjects with the following diagnoses: Normal, 11.8%; Mild cognitive impairment, 44.6%; Alzheimer's disease, 34.9%; and other dementias, 8.7%. Overall, 35% used AChEIs and 13% used memantine. AChEI and memantine use was greater in subjects who were referred by clinics and diagnosed with Alzheimer's disease. AChEI use was associated with being married, younger, male, and more educated while memantine use was associated with less severe apathy and other dementia diagnosis. Non-Hispanic whites were more likely to use AChEI and memantine than non-Hispanic blacks (OR = 2.2, 2.5). Hispanics were more likely to use AChEI than non-Hispanic blacks. It appears anti-dementia medication use in CDR 0.5 is frequent and represents evidence for extensive off label usage. Diagnosis, severity of impairment, and race, among other variables, affect the likelihood of AChEI and memantine use in this population.

Factors affecting usage patterns of memantine in Alzheimer disease.

Memantine is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer disease (AD). We investigated the frequency and variables associated with its use in mild to moderate/severe AD as defined by criteria involving the Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) scale. Consecutive possible and probable AD patients seen at our research center from November 2003 to December 2006 were included. Individuals were classified as mild dementia either by CDR=1 or MMSE >or=15, using criteria derived in part from the pivotal trials of memantine used for its approval by the Food and Drug Administration. Of 117 patients, 37% of those with mild AD by MMSE criterion (total N=94), and 38% of those with mild AD by CDR criterion (total N=86) used memantine. Logistic regression was used to simultaneously estimate the odds ratios (ORs) of the likelihood of memantine usage associated with a set of predictor variables. Lower MMSE was associated with a greater likelihood of using memantine independent of CDR [ORMMSE=7.45, 95% confidence interval (CI)=1.50-37.05]; CDR was not significantly related to memantine use. Controlling both MMSE and CDR, Whites were more likely to use memantine than African Americans (OR=6.47, 95% CI=1.25-33.39). Patients who used other antidementia medications were more likely to use memantine than those who did not (OR=3.15, 95% CI=0.995-9.97). Eight other patient characteristics were not significant predictors. Use of memantine in mild AD was common. Patterns of memantine usage are complex and deserve further study in a larger sample because of their implications for medical system cost, equitable access to care, and risk of drug interactions.

Asymmetric recovery in cerebellar-deficient mice following unilateral labyrinthectomy.

The term "vestibular compensation" refers to the resolution of motor deficits resulting from a peripheral vestibular lesion. We investigated the role of the cerebellum in the compensation process by characterizing the vestibuloocular reflex (VOR) evoked by head rotations at frequencies and velocities similar to those in natural behaviors in wild-type (WT) versus cerebellar-deficient Lurcher (Lc/+) mice. We found that during exploratory activity, normal mice produce head rotations largely consisting of frequencies < or =4 Hz and velocities and accelerations as large as 400 degrees/s and 5,000 degrees/s2, respectively. Accordingly, the VOR was characterized using sinusoidal rotations (0.2-4 Hz) as well as transient impulses (approximately 400 degrees/s; approximately 2,000 degrees/s2). Before lesions, WT and Lc/+ mice produced similar VOR responses to sinusoidal rotation. Lc/+ mice, however, had significantly reduced gains for transient stimuli. After unilateral labyrinthectomy, VOR recovery followed a similar course for WT and Lc/+ groups during the first week: gain was reduced by 80% for ipsilesionally directed head rotations on day 1 and improved for both strains to values of approximately 0.4 by day 5. Moreover, responses evoked by contralesionally directed rotations returned to prelesion in both strains within this period. However, unlike WT, which showed improving responses to ipsilesionally directed rotations, recovery plateaued after first week for Lc/+ mice. Our results show that despite nearly normal recovery in the acute phase, long-term compensation is compromised in Lc/+. We conclude that cerebellar pathways are critical for long-term restoration of VOR during head rotation toward the lesioned side, while noncerebellar pathways are sufficient to restore proper gaze stabilization during contralesionally directed movements.

Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life.

PURPOSE: According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues. DESIGN AND METHODS: 349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables. RESULTS: Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education. Verbal fluency, in contrast, was affected by adolescent IQ through links with high school mental activities, but not education. IMPLICATIONS: Our study suggests that reserve is dynamic, but it is most amenable to change in early life. We conclude that an active, engaged lifestyle, emphasizing mental activity and educational pursuits in early life, can have a positive impact on cognitive functioning in late life.

Bone breccias, bone dumps, and sedimentary sequences of the western Limeworks, Makapansgat, South Africa.

The sediments in the western side of the Makapansgat Limeworks were either precipitated as speleothems, represented in the earlier massive deposits, or were deposited as coarsening clastic sediments, mainly representing later deposits. Between the earlier deposits and the main sedimentary phase, the stratigraphic sequence was inverted twice to a considerable height by the unusual deposition of subaqueous speleothem. Bone-bearing deposits, including the Main Quarry Bone Breccia and the well-known Grey Breccia belong, in time, to the lower part of the clastic deposits called the Red Silts. Australopith fossils have been found in the Grey Breccia dumped material and, in situ, from the dolomite clast breccia on the Main Quarry entrance buttress. Whatever the problems may be in provenancing some of the material from the Limeworks dumps, there is no doubt that the three rows of blocks on the southern side of the dumps belong to the Grey Breccia, and other rows contain red sediment sufficient for them to be safely associated with the Red Silts. There is no reason why this material should not be prepared with confidence as to its stratigraphic provenance. In any case, stratigraphic evidence, presented here, shows that there is little difference in time between the deposition of the bone-bearing breccias.